Structure and function of the cerebrovasculature is critical for ischemic stroke outcome. We showed that diabetes causes cerebrovascular remodeling by activation of the endothelin A (ET(A)) receptors. The goal of this study was to test the hypotheses that vasculoprotective endothelial ET(B) receptors are decreased and pharmacological inhibition of the ET(B) receptor augments vascular remodeling...

The present study was performed to evaluate the role of an interaction between the endothelin (ET) and the renin-angiotensin systems (RAS) in the development and maintenance of hypertension and in hypertension-associated end-organ damage in heterozygous male and female transgenic rats harboring the mouse Ren-2 renin gene (TGR). Twenty-eight days old heterozygous TGR and age-matched transgene-ne...

Bacterial infections induce exacerbations in chronic lung diseases, e.g., chronic obstructive pulmonary disease (COPD), by enhancing airway inflammation. Exacerbations are frequently associated with right heart decompensation and accelerate disease progression. Endothelin receptor antagonists (ERAs) might have therapeutic potential as pulmonary vasodilators and anti-inflammatory agents, but uti...

Recent studies suggest that endogenous endothelin mediates much of the vasoconstrictor activity and vascular fibrotic damage caused by chronic administration of angiotensin II. The present study uses the mixed endothelin-A and endothelin-B receptor antagonist bosentan and the endothelin-A-selective blocker BQ-123 to study the contribution of endogenous endothelin to the pressor and renal action...

OBJECTIVES Intimal hyperplasia is a major reason for the restenosis of vein grafts. A vascular external sheath was designed to inhibit intimal hyperplasia of vein grafts. METHODS Using the biodegradable material poly(lactic-co-glycolic acid) and fibrin, a high porosity external sheath carrying bosentan with a stratified internal spiral structure was made by grouping mould extraction and low-t...

BACKGROUND Bosentan improves symptoms in patients with Eisenmenger syndrome (ES). This study evaluated the effect of long-term bosentan therapy on cardiac function and its relation to symptomatic benefits in ES patients. METHODS AND RESULTS Twenty-three consecutive adult ES patients (15 with ventricular septal defect, 6 with atrial septal defect, and 2 with patent ductus arteriosus) underwent...

BACKGROUND Endothelin (ET) is one of the most important contributing factors in the pathophysiology of cardiovascular diseases. However, little is known about its role in myocarditis. METHODS AND RESULTS Four-week-old DBA/2 mice were inoculated with the encephalomyocarditis virus. Expression levels of ET-converting enzyme-1 (ECE-1) and prepro-ET-1 mRNA were significantly increased at 7 and 14...

OBJECTIVE(S) To investigate the clinical and cost-effectiveness of epoprostenol, iloprost, bosentan, sitaxentan and sildenafil for the treatment of adults with pulmonary arterial hypertension (PAH) within their licensed indications. DATA SOURCES Major electronic databases (including the Cochrane Library, MEDLINE and EMBASE) were searched up to February 2007. Further data were obtained from do...

Cytochrome P450 (P450) 2C9 is an important member of the P450 enzyme superfamily, with 58 CYP2C9 allelic variants previously reported. Genetic polymorphisms of CYP2C9 significantly influence the efficacy and safety of some drugs, which might cause adverse effects and therapeutic failure. The aim of this study was to assess the catalytic activities of 38 human CYP2C9 alleles, including 24 novel ...